{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:37:42Z","timestamp":1792075062469,"version":"4.4.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:00:00Z","timestamp":1682294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"\n Background<\/jats:title>\n Antimicrobial resistance is a serious threat to public health globally. It is a slower-moving pandemic than COVID-19, so we are fast running out of treatment options.<\/jats:p>\n <\/jats:sec>\n \n Purpose<\/jats:title>\n Thus, this study was designed to search for an alternative biomaterial with broad-spectrum activity for the treatment of multidrug-resistant (MDR) bacterial and fungal pathogen-related infections.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We isolated\n Streptomyces<\/jats:italic>\n species from soil samples and identified the most active strains with antimicrobial activity. The culture filtrates of active species were purified, and the bioactive metabolite extracts were identified by thin-layer chromatography (TLC), preparative high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and gas chromatography-mass spectrometry (GC-MS). The minimum inhibitory concentrations (MICs) of the bioactive metabolites against MDR bacteria and fungi were determined using the broth microdilution method.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Preliminary screening revealed that\n Streptomyces misakiensis<\/jats:italic>\n and\n S. coeruleorubidus<\/jats:italic>\n exhibited antimicrobial potential. The MIC\n 50<\/jats:sub>\n and MIC\n 90<\/jats:sub>\n of S. misakiensis antibacterial bioactive metabolite (ursolic acid methyl ester) and antifungal metabolite (tetradecamethylcycloheptasiloxane) against all tested bacteria and fungi were 0.5 \u03bcg\/ml and 1 \u03bcg\/mL, respectively, versus\n S. coeruleorubidus<\/jats:italic>\n metabolites: thiocarbamic acid,\n N,N<\/jats:italic>\n -dimethyl, S-1,3-diphenyl-2-butenyl ester against bacteria (MIC\n 50<\/jats:sub>\n : 2 \u03bcg\/ml and MIC\n 90<\/jats:sub>\n : 4 \u03bcg\/mL) and fungi (MIC\n 50<\/jats:sub>\n : 4 \u03bcg\/ml and MIC\n 90<\/jats:sub>\n : 8 \u03bcg\/mL). Ursolic acid methyl ester was active against ciprofloxacin-resistant strains of\n Streptococcus pyogenes<\/jats:italic>\n ,\n S. agalactiae<\/jats:italic>\n ,\n Escherichia coli, Klebsiella pneumoniae<\/jats:italic>\n , and\n Salmonella<\/jats:italic>\n enterica serovars, colistin-resistant\n Aeromonas hydrophila<\/jats:italic>\n and\n K. pneumoniae<\/jats:italic>\n , and vancomycin-resistant\n Staphylococcus aureus<\/jats:italic>\n . Tetradecamethylcycloheptasiloxane was active against azole- and amphotericin B-resistant\n Candida albicans<\/jats:italic>\n ,\n Cryptococcus neoformans<\/jats:italic>\n ,\n C. gattii, Aspergillus flavus, A. niger<\/jats:italic>\n , and\n A. fumigatus<\/jats:italic>\n . Ursolic acid methyl ester was applied\n in vivo<\/jats:italic>\n for treating\n S. aureus<\/jats:italic>\n septicemia and\n K. pneumoniae<\/jats:italic>\n pneumonia models in mice. In the septicemia model, the ursolic acid methyl ester-treated group had a significant 4.00 and 3.98 log CFU\/g decrease (\n P<\/jats:italic>\n &lt; 0.05) in liver and spleen tissue compared to the infected, untreated control group. Lung tissue in the pneumonia model showed a 2.20 log CFU\/g significant decrease in the ursolic acid methyl ester-treated group in comparison to the control group. The haematological and biochemical markers in the ursolic acid methyl ester-treated group did not change in a statistically significant way. Moreover, no abnormalities were found in the histopathology of the liver, kidneys, lungs, and spleen of ursolic acid methyl ester-treated mice in comparison with the control group.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n S. misakiensis<\/jats:italic>\n metabolite extracts are broad-spectrum antimicrobial biomaterials that can be further investigated for the potential against MDR pathogen infections. Hence, it opens up new horizons for exploring alternative drugs for current and reemerging diseases.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fcimb.2023.1162721","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T00:32:10Z","timestamp":1682296330000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Bioactive metabolites of Streptomyces misakiensis display broad-spectrum antimicrobial activity against multidrug-resistant bacteria and fungi"],"prefix":"10.3389","volume":"13","author":[{"given":"Rewan","family":"Abdelaziz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine H.","family":"Tartor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed B.","family":"Barakat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal","family":"EL-Didamony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa M.","family":"Gado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adina","family":"Berbecea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habil dr. 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